ImmunityBio announced its COVID-19 vaccine candidate protected nasal and lung airways of non-human primates against coronavirus (SARS-CoV-2) in a challenge study. The study, sponsored by the Biomedical Advanced Research & Development Authority (BARDA), provides evidence supporting the company’s use of a second-generation adenoviral vector that induces the immune system to both activate T cells and generate antibodies against multiple viral targets—blocking virus replication and clearing existing infection.
In the study, immunisation with the hAd5-COVID-19 vaccine inhibited SARS-CoV-2 virus replication in 100 per cent (10 of 10) of Rhesus macaques, with a drop in viral replication starting on the first day of vaccine administration, and undetectable viral levels as early as three to five days post-challenge in most of the animals. The vaccine targeted both the inner nucleocapsid (N) and the outer spike (S) proteins of the virus to maximise the immune response. The goal of targeting both S and N was to both activate virus-specific T cells and generate anti-SARS-CoV-2-neutralizing antibodies. The study showed this broad immune response led to the complete clearance of the virus in a matter of days after infection of previously-vaccinated primates. This blocking of viral replication was observed in both the lung and nasal passages. By protecting the nasal passages (the primary point of entry for the virus), the vaccine has the potential to reduce reinfection. Clearing replicating viruses from nasal passages is critical for reducing transmission of the virus from immunised recipients to others.
The hAd5-COVID-19 candidate is designed to address a potential problem that may emerge when first-generation adenoviral platforms are used as vaccine vectors: vaccine inactivation due to pre-existing immunity to the vector itself. This risk exists for many vaccine candidates being tested in Europe, China, Russia, and the United States. Many people who have been exposed to the “common cold” potentially develop adenovirus immunity: the immune system often attacks and disables these first-generation vaccines before they can activate the immune response to attack the SARS-CoV-2 virus. This can significantly limit the effectiveness of first-generation platforms. ImmunityBio has engineered the vector to overcome this problem and has shown that its second-generation adenovirus vector can safely and effectively deliver its cargo even in patients with pre-existing adenovirus immunity.
“These results provide compelling evidence of the need for vaccines to target both S and N proteins and to activate T cells to produce immune system memory to combat this virus. The adage that ‘B cells forget but T cells remember’ has never been more important, and leveraging the S plus N combination has resulted in a vaccine that is not only showing evidence of being effective but also one that has the potential to provide long-term T-cell memory. The exciting finding that the thermally-stable oral formulation triggers immune responses sufficient to inhibit virus replication to undetectable levels bodes well for the possibility that this oral formulation could serve as a universal heterologous booster. Our oral capsule could be a solution to the enormous challenges facing cold chain logistics and enable global distribution of the vaccine,” said Patrick Soon-Shiong, MD, Chairman and CEO of ImmunityBio.
This study was designed to test the safety, immunogenicity and protection from infection and disease provided by ImmunityBio’s hAd5-COVID-19 vaccine. The vaccine was administered in two separate regimens. In the first, primates received subcutaneous (SC) vaccination on Day 0, followed by an SC boost on Day 14 and an oral boost on Day 28. In the second, the SC prime was followed by two oral boosts on the same schedule. Placebo controls were used for comparison for both. Subcutaneous injection of hAd5 and oral administration of enteric-coated capsules in Rhesus macaques did not result in any treatment-related toxicities.